FIDES-01: Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

Basilea Pharmaceutica (Industry)
Overall Status
Recruiting ID
Anticipated Duration (Months)
Patients Per Site
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of derazantinib by Objective Response Rate (ORR) by central radiology review as per RECIST v1.1 in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) whose tumors harbor FGFR2 gene fusions (by FISH performed by the central laboratory) or FGFR2 gene mutations or amplifications (based on NGS testing performed or commissioned by the respective study center) and who received at least one prior regimen of systemic therapy. Subjects will be dosed orally once per day at 300 mg of derazantinib capsules.

Study Design

Study Type:
Anticipated Enrollment :
143 participants
Intervention Model:
Single Group Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Pivotal Study of Derazantinib in Patients With Inoperable or Advanced Intrahepatic Cholangiocarcinoma and FGFR2 Gene Fusions or FGFR2 Gene Mutations or Amplifications
Actual Study Start Date :
Nov 10, 2017
Anticipated Primary Completion Date :
Jun 30, 2022
Anticipated Study Completion Date :
Jun 30, 2022

Arms and Interventions

Experimental: derazantinib

Oral administration

Drug: derazantinib
derazantinib will be orally administered at 300 mg once per day one hour prior to or two hours after a meal and is supplied as 100 mg capsules.

Outcome Measures

Primary Outcome Measures

  1. Substudy 1: Anti-cancer activity of derazantinib by Objective Response Rate (ORR) [Up to approximately 32 weeks]

    ORR will be assessed by central radiology review as per RECIST version 1.1

  2. Substudy 2: Anti-tumor activity of derazantinib by Progression Fress Survival at 3 months (PFS 3) [3 months]

    PFS 3 will be assessed based on survival status or central radiology review (Response Evaluation Criteria in Solid Tumors, RECIST 1.1)

Secondary Outcome Measures

  1. Safety of derazantinib as assessed by adverse events [Up to approximately 36 weeks]

    Adverse events will be graded using NCI CTCAE guidelines, version 4.03

  2. Anti-cancer activity of derazantinib by duration of response (DoR) [Up to approximately 32 weeks]

    DoR will be assessed by central radiology review per RECIST version 1.1

  3. Anti-cancer activity of derazantinib by progression free survival (PFS) [Up to approximately 32 weeks]

    PFS will be assessed by central radiology review per RECIST version 1.1

  4. Anti-cancer activity of derazantinib by overall survival (OS) [Up to approximately 36 weeks]

    OS will be calculated from the first date of receiving study drug until death

  5. Health-related quality of life as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire [Up to approximately 36 weeks]

  6. Health-related quality of life as assessed by the EORTC QLQ-BIL21 questionnaire [Up to approximately 36 weeks]

  7. Health-related quality of life as assessed by the EuroQol EQ-5D questionnaire [Up to approximately 36 weeks]

  8. Substudy 2: Anti-cancer activity of derazantinib by Objective Response Rate [Up to approximately 32 weeks]

    ORR will be assessed by central radiology review as per RECIST version 1.1

Eligibility Criteria


Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  1. Signed written informed consent granted prior to initiation of any study-specific procedures

  2. 18 years of age or older

  3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA])

  4. Substudy 1: FGFR2 fusion status based on the following assessments:

  1. If central laboratory designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients may be enrolled and may start dosing, but central confirmation is required* ii) Negative FISH or NGS test: tissue may be submitted to the central laboratory designated by the Sponsor, and patients may only be enrolled if the central test is positive

*Using standard protocols and approved by local IRB/EC, by CLIA or other similar agency.

Substudy 2: FGFR2 mutation/amplification status based on local NGS testing performed or commissioned by the respective study site.

  1. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression

  2. Measurable disease by RECIST version 1.1 criteria

  3. ECOG performance status ≤ 1

  4. Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory).

  • Hematological

  • Hemoglobin (Hgb) ≥ 9.0 g/dL

  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

  • Platelet count ≥ 75 x 109/L

  • International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin

  • Hepatic

  • Total bilirubin ≤ 2 x ULN

  • AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)

  • Albumin ≥ 2.8 g/dL

  • Renal

  • Serum creatinine ≤ 1.5 x ULN

  • Creatinine clearance of ≥ 30 mL/min as estimated by the Cockcroft-Gault equation

  1. Female and male patients of child-producing potential must agree to avoid becoming pregnant or impregnating a partner, respectively, use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse, during the study*, and until at least 120 for 90 days after the last dose of derazantinib.

*From the day of first study medication, or for oral contraception from 14 days before first study medication.

Male patients are considered not to be of child-producing potential if they have azoospermia (whether due to vasectomy or an underlying medical condition). Female patients are considered not to be of child-producing potential if they are:

  • postmenopausal* , or

  • have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening, or

  • have a congenital or acquired condition that prevents childbearing.

Male or female patients of child-producing potential must agree to comply with one of the following until at least 120 days after the last dose of derazantinib:

  1. Abstinence from heterosexual activity**

  2. Using (or having their partner use) an acceptable method of contraception during heterosexual activity. Acceptable methods of contraception are***:

  • any ONE of:

  • an intrauterine device (IUD)

  • vasectomy of a female patient's male partner

  • a contraceptive rod implanted into the skin.

  • any TWO in combination of:

  • diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)

  • cervical cap with spermicide (nulliparous women only)

  • contraceptive sponge (nulliparous women only)

  • male condom or female condom (cannot be used together)

  • hormonal contraceptive (oral contraceptive pill [estrogen/progestin pill or progestin-only pill], contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection)

*Postmenopausal is defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post -menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is not sufficient.

  • Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

  • If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as an acceptable method of contraception for subjects participating at sites in this country/region.

Exclusion Criteria:
  1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
  • One chemotherapy or biological (e.g., antibody) cycle interval

  • Five half-lives of any small-molecule investigational or licensed medicinal product

  • Two weeks, for any investigational medicinal product with an unknown half-life

  • Four weeks of curative radiotherapy

  • Seven days of palliative radiotherapy

  • 28 days of radiotherapy

  1. Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib

  2. Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).

  • Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate
  1. Unable or unwilling to swallow the complete daily dose of derazantinib capsules

  2. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)

  3. Current evidence of clinically significant corneal or retinal disorder likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination.

  4. Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of derazantinib)

  5. History of significant cardiac disorders:

  • Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of derazantinib (MI that occurred > 6 months prior to the first dose of derazantinib will be permitted)

  • QTcF >450 msec (males or females)

  1. Serum electrolyte abnormalities defined as follows:
  • Hyperphosphataemia: Serum phosphate > institutional ULN

  • Hyperkalemia: > 6.0 mmol/L

  • Hypokalemia: < 3.0 mmol/L

  • Hypercalcemia: corrected serum calcium < 1.75 mmol/L (< 7.0 mg/dL)

  • Hypocalcemia: corrected serum calcium > 3.1 mmol/L (> 12.5 mg/dL)

  • Hypomagnesemia: < 0.4 mmol/L (< 0.9 mg/dL)

  1. Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of derazantinib (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)

  2. History of additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.

  3. Concurrent uncontrolled illness not related to cancer, including but not limited to:

  • Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements

  • Known uncontrolled human immunodeficiency virus (HIV) infection

  • Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration

  1. Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility

  2. Pregnant or breast feeding

  3. Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate)

Contacts and Locations


SiteCityStateCountryPostal Code
1Mayo ClinicPhoenixArizonaUnited States85054
2Mayo ClinicJacksonvilleFloridaUnited States32224
3Moffitt Cancer CenterTampaFloridaUnited States33612-9416
4Winship Cancer Institute of Emory UniversityAtlantaGeorgiaUnited States30322
5Mayo ClinicRochesterMinnesotaUnited States55905
6Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic CancersNew YorkNew YorkUnited States10065-6800
7Abramson Cancer Center of the University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
8Vanderbilt-Ingram Cancer CenterNashvilleTennesseeUnited States37232
9The University of Texas Southwestern Medical CenterDallasTexasUnited States75390
10University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030
11University of Washington Medical CenterSeattleWashingtonUnited States98109
12Hôpital ErasmeBrusselsBelgium1070
13Cliniques Universitaires Saint-LucBrusselsBelgium1200
14Antwerp University HospitalEdegemBelgium2650
15Tom Baker Cancer CentreCalgaryAlbertaCanadaT2N 4N2
16Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9
17CHU Grenoble AlpesLa TroncheFrance38700
18Gustave RoussyVillejuifFrance94805
19Universitätsklinikum FrankfurtFrankfurt am MainGermany60590
20Universitätsklinikum Hamburg-Eppendorf (UKE)HamburgGermany20246
21Medizinische Hochschule Hannover (MHH)HannoverGermany30625
22Universitätsklinikum des SaarlandesHomburgGermany66421
23Universitätsmedizin der Johannes Gutenberg-Universität MainzMainzGermany55131
24St. James's HospitalDublinIrelandD08 NHY1
25Sant'Orsola-Malpighi Hospital, University of BolognaBolognaItaly40138
26Fondazione IRCCS Istituto Nazionale dei TumoriMilanItaly20133
27Ospedale San GerardoMonzaItaly20900
28Istituto Oncologico Veneto - IRCCSPadovaItaly35128
29Azienda Ospedaliero-Universitaria PisanaPisaItaly56126
30Humanitas Cancer Center, Istituto Clinico Humanitas IRCCSRozzanoItaly20089
31Seoul National University HospitalSeoulKorea, Republic of3080
32Samsung Medical CenterSeoulKorea, Republic of6351
33The Catholic University of Korea, Seoul St. Mary's HospitalSeoulKorea, Republic of6591
34Vall d'Hebrón University HospitalBarcelonaSpain08035
35Catalan Institute of OncologyBarcelonaSpain08908
36Hospital General Universitario Gregorio MarañónMadridSpain28007
37Hospital Universitario 12 de OctubreMadridSpain28041
38Universitätsspital BaselBaselSwitzerland4031
39University College London Hospitals NHS Foundation TrustEustonUnited KingdomNW1 2BU
40Beatson West of Scotland Cancer CentreGlasgowUnited KingdomG120YN
41The Royal MarsdenSuttonUnited KingdomSM2 5PT

Sponsors and Collaborators

  • Basilea Pharmaceutica


  • Study Director: Miryana Dimova-Dobreva, MD, Basilea Pharmaceutica International Ltd

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
Basilea Pharmaceutica Identifier:
Other Study ID Numbers:
  • DZB-CS-301
  • ARQ 087-301
First Posted:
Jul 26, 2017
Last Update Posted:
Mar 8, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by Basilea Pharmaceutica
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 8, 2022